# Structural characterization and inhibition of the interaction between ch-TOG and TACC3

## TL;DR

Scientists discovered how two proteins, TACC3 and ch-TOG, interact during cell division and developed a tool to block this interaction, revealing its role in maintaining cell division structures.

## Contribution

The study provides a structural model of TACC3 and ch-TOG interaction and introduces Affimers to inhibit it, uncovering a new role in mitotic pericentriolar material integrity.

## Key findings

- The α-helical bundle domain of ch-TOG interacts with TACC3, as revealed by structural and biochemical data.
- Affimers targeting TACC3's ch-TOG-binding site disrupt the interaction without affecting other proteins.
- Inhibiting the TACC3–ch-TOG interaction causes pericentriolar material fragmentation and delays mitosis.

## Abstract

Shelford, Burgess, and colleagues present a structural model of the interaction between TACC3 and ch-TOG. They discover Affimers that can inhibit this interaction and show that in cells, inhibiting the TACC3–ch-TOG interaction causes fragmentation of the mitotic pericentriolar material.

The mitotic spindle is a bipolar array of microtubules, radiating from the poles which each contain a centrosome, embedded in pericentriolar material. Two proteins, ch-TOG and TACC3, have multiple functions at the mitotic spindle due to operating either alone, together, or in complex with other proteins. To distinguish these activities, we need new molecular tools to dissect their function. Here, we present the structure of the α-helical bundle domain of ch-TOG that mediates its interaction with TACC3 and a structural model describing the interaction, supported by biophysical and biochemical data. We have isolated Affimer tools to precisely target the ch-TOG-binding site on TACC3 in live cells, which displace ch-TOG without affecting the spindle localization of other protein complex components. Inhibition of the TACC3–ch-TOG interaction led unexpectedly to fragmentation of the pericentriolar material in metaphase cells and delayed mitotic progression, uncovering a novel role of TACC3–ch-TOG in maintaining pericentriolar material integrity during mitosis to ensure timely cell division.